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Background People with severe mental illness have a higher rate of premature death than the general population, largely due to primary care preventable diseases. There has been little research on the health profile of this population attending Australian general practices. Methods In this nationwide cross-sectional study, MedicineInsight data for adult patients regularly attending general practices in 2018 were analysed to estimate the prevalence of schizophrenia or bipolar disorders (SBD) and investigate the health profile of people with SBD compared with other patients. Multilevel models clustered by practice (n = 565) and patient, and practice characteristics were created. Results The prevalence of recorded SBD was 1.91% (95% CI = 1.88%–1.94%) among the 618 849 patients included. Patients with recorded SBD were more likely than other patients to have records of health risk factors, particularly smoking (aOR = 3.8, 95% CI = 3.6–3.9) and substance use (aOR = 5.9, 95% CI = 5.6–6.3), and higher probabilities of comorbidities including cardiovascular diseases (aOR = 1.3, 95% CI = 1.2–1.4), cancer (aOR = 1.1, 95% CI = 1.0–1.2), diabetes mellitus type 2 (aOR = 2.2, 95% CI = 2.0–2.3), chronic kidney diseases (aOR = 1.7, 95% CI = 1.5–2.0), chronic liver diseases (aOR = 3.3, 95% CI = 2.6–4.0) and chronic respiratory diseases (aOR = 1.7, 95% CI = 1.7–1.8). Conclusions The higher prevalence of health risk factors and comorbidities among patients with recorded SBD underscores the need for proactive health risk monitoring and preventive care to address this health inequity.

Pharmacy dispensing data are useful for estimating adherence to therapy. Here, we implement multiple adherence measures to antiretroviral therapy (ART) and provide an online tool for visualising results. We conducted a cohort study for 2,042 people dispensed ART in Australia. We assessed adherence using the Proportion of Days Covered (PDC) within 360 days of follow-up as a continuous measure and dichotomised (PDC ≥80%). We defined a covered day as the 1) exposure to ≥3 antiretrovirals at the same time 2) exposure to any antiretroviral 3) lowest number of days covered per antiretroviral 4) average of days covered over all antiretrovirals 5) highest number of days covered per antiretroviral. For each method, we conducted sensitivity analyses. The median PDC ranged between 93.3%-98.3%. Between 67.0%-87.7% of individuals were classified as adherent, with higher values for measure 2 (85.5%-89.7%) and lower values for measure 3 (67.0%-70.9%). Censoring loss to follow-up had a higher impact on adherence estimates than considering a grace period. The variation in adherence estimates can be substantial, especially when dichotomising adherence. Researchers should consider operationalising multiple measures to estimate adherence bounds and identify a range of people at risk of non-adherence for targeted interventions.

Background: Depression and anxiety affect 4–14% of Australians every year; symptoms may have been exacerbated during the COVID-19 pandemic. We examined recent patterns of antidepressant use in Australia in the period 2015–2021, which includes the first year of the pandemic. Methods: We used national dispensing claims for people aged ⩾10 years to investigate annual trends in prevalent and new antidepressant use (no antidepressants dispensed in the year prior). We conducted stratified analyses by sex, age group and antidepressant class. We report outcomes from 2015 to 2019 and used time series analysis to quantify changes during the first year of the COVID-19 pandemic (March 2020–February 2021). Results: In 2019, the annual prevalence of antidepressant use was 170.4 per 1000 women and 101.8 per 1000 men, an increase of 7.0% and 9.2% from 2015, respectively. New antidepressant use also increased for both sexes (3.0% for women and 4.9% for men) and across most age groups, particularly among adolescents (aged 10–17 years; 46–57%). During the first year of the COVID-19 pandemic, we observed higher than expected prevalent use (+2.2%, 95% CI = [0.3%, 4.2%]) among females, corresponding to a predicted excess of 45,217 (95% CI = [5,819, 84,614]) females dispensed antidepressants. The largest increases during the first year of the pandemic occurred among female adolescents for both prevalent (+11.7%, 95% CI = [4.1%, 20.5%]) and new antidepressant use (+15.6%, 95% CI = [8.5%, 23.7%]). Conclusion: Antidepressant use continues to increase in Australia overall and especially among young people. We found a differential impact of the COVID-19 pandemic in treated depression and anxiety, greater among females than males, and greater among young females than other age groups, suggesting an increased mental health burden in populations already on a trajectory of increased use of antidepressants prior to the pandemic. Reasons for these differences require further investigation.

We quantified concomitant medicine use and occurrence of potential drug-drug interactions in people living with HIV in Australia who are treated with antiretroviral therapy (ART).In this cohort study using dispensing claims of a 10% random sample of Australians, we identified 2230 people dispensed ART between January 2018 and December 2019 (mean age 49.0 years, standard deviation 12.0 years, 88% male). We examined concomitant medicine use by identifying nontopical medicines dispensed within 90-days of any antiretroviral medicine dispensing during a 12-month follow-up period. For every antiretroviral and nonantiretroviral pair, we identified and classified possible drug-drug interactions using the University of Liverpool HIV drug interactions database.A total of 1728 (78%) people were dispensed at least 1 and 633 (28%) 5 or more unique medicines in addition to ART in a 12-month period; systemic anti-infectives and medicines acting on the nervous system were the most common (68% and 56%, respectively). Among comedicated people, 1637 (95%) had at least 1 medicine combination classified as weak interactions, 558 (32%) interactions requiring close monitoring/dose adjustment and 94 (5%) that should not be coadministered. Contraindication or interactions requiring close monitoring/dose adjustment were more common among people receiving protease inhibitors (50-73% across different antiretrovirals), non-nucleoside reverse transcriptase inhibitors (35-64%), people using single-tablet combinations containing elvitegravir (30-46%) and those using tenofovir disoproxil (26-30%).Concomitant medicine use is widespread among people living with HIV in Australia. Despite a relatively low prevalence of contraindicated medicines, almost a third received medicines that require close monitoring or dose adjustment.

Neisseria meningitidis serogroup B (MenB) is the most common cause of meningococcal disease in adolescents and young adults. In Australia, MenB vaccination has been available through private prescription since 2014 and has been recommended for at-risk groups including adolescents, young adults who smoke and people medically at risk. For each of these at-risk groups, we estimated cumulative annual coverage of MenB vaccination between 2014 and 2019. We also evaluated factors associated with vaccination coverage in 2019. Our analyses used electronic health records in the national MedicineInsight database for people regularly attending general practices. Cumulative vaccination coverage increased among the at-risk groups between 2014 and 2019: from 0.09% to 1.65% for adolescents, from 0.01% to 0.15% for young adults who smoke, and from 0.35% to 12.09% for people medically at risk. However, vaccination coverage in 2019 remained very low across these groups. Data sparsity prevented the evaluation of factors associated with vaccination coverage for smokers. We observed variation in the relative risk of being vaccinated by age, sex, socioeconomic and clinical factors for adolescents and people medically at risk. Still, the absolute magnitude of coverage was low across all subgroups examined, and indicates a need for strategies to increase vaccination uptake among at-risk groups irrespective of patient and practice characteristics. Our study provides baseline data for monitoring menB vaccination uptake among recommended groups in light of limited national data, especially for medically at-risk groups.

Routinely collected data have been increasingly used to assess long-term opioid therapy (LTOT) patterns, with very little guidance on how to measure LTOT from these data sources. We conducted a systematic review of studies published between January 2000 and July 2019 to catalogue LTOT definitions, the rationale for definitions and LTOT rates in observational research using routinely collected data in nonsurgical settings. We screened 4056 abstracts, 210 full-text manuscripts and included 128 studies, mostly from the United States (81%) and published between 2015 and 2019 (69%). We identified 78 definitions of LTOT, commonly operationalised as 90 days of use within a year (23%). Studies often used multiple criteria to derive definitions (60%), mostly based on measures of duration, such as supply days/days of use (66%), episode length (21%) or prescription fills within specified time periods (12%). Definitions were based on previous publications (63%), clinical judgment (16%) or empirical data (3%); 10% of studies applied more than one definition. LTOT definition was not provided with enough details for replication in 14 studies and 38 studies did not specify the opioids evaluated. Rates of LTOT within study populations ranged from 0.2% to 57% according to study design and definition used. We observed a substantial rise in the last 5 years in studies evaluating LTOT with large variability in the definitions used and poor reporting of the rationale and implementation of definitions. This variation impacts on research reproducibility, comparability of findings and the development of strategies aiming to curb therapy that is not guideline-recommended.

We examined trends in the prevalence of post-exposure prophylaxis following sexual exposure (PEPSE) per million population (2011-2019) and the proportion of repeated PEPSE within 365 days of the first PEPSE dispensing (2011-2018) in Brazil. We also compared the prevalence of repeated PEPSE according to patient and health services characteristics in 2018. The prevalence of PEPSE increased 55.5% from 2011 to 2019. Repeated PEPSE increased 11.8%, reaching 8.4% among people with their first dispensing in 2018. The prevalence of repeated PEPSE was higher in cis men or trans women (versus cisgender women); homosexuals (versus heterosexuals); and people aged 25-29 years (versus other age groups). We also observed greater prevalence of repeated PEPSE in HIV services in populous cities or services with elevated caseloads. Our findings highlight the need for strategies to reduce repeated PEPSE and promote other HIV-prevention technologies, particularly among young adults, cisgender men, transgender women, and homosexuals.Examinamos las tendencias de la prevalencia de uso de la profilaxis posterior a la exposición sexual (PEPSE) por millón de población (2011–2019) y la proporción de PEPSE repetida dentro de los 365 días de la primera dispensación de PEPSE (2011–2018) en Brasil. También comparamos la prevalencia de PEPSE repetida según las características del paciente y de los servicios de salud en 2018. La prevalencia de PEPSE aumentó un 55,5% de 2011 a 2019. La PEPSE repetida aumentó un 11,8%, alcanzando el 8,4% entre las personas con su primera dispensación en 2018. La prevalencia de PEPSE repetida fue mayor en hombres cis o mujeres trans (versus mujeres cisgénero); homosexuales (versus heterosexuales); y personas de 25 a 29 años (versus otros grupos de edad). También observamos una mayor prevalencia de repetición en los servicios de VIH de las ciudades más pobladas o con un elevado número de clientes. Nuestros hallazgos ponen de manifiesto la necesidad de estrategias para reducir la repetición de la PEPSE y promover otras tecnologías de prevención del VIH entre los adultos jóvenes, especialmente los hombres, las trans y los homosexuales.

The lifetime use of combination antiretroviral therapy (cART) highlights the need to understand patterns of and factors associated with adherence to cART. In this cohort study using a 10% random sample of dispensing claims data for eligible Australians, we identified 2042 people dispensed cART between January 2016 and December 2017 (mean age 48.0 ± 12.0 years old, 88.6% male, and 85.9% treatment experienced). We considered people to be adherent if the proportion of treatment coverage days was ≥80% in the 360 days after their first observed cART dispensing. We also used group-based trajectory modeling (GBTM) to examine different patterns of adherence for 360 days from first observed cART dispensing. Most commonly, people receiving cART were treated with two nucleoside/nucleotide reverse transcriptase inhibitors with an integrase strand transfer inhibitors (INSTI-46.6%). Overall, 1708 people [83.6% (95% confidential interval 82.0-85.3%)] remained adherent over 360 days. GBTM identified three distinct adherence patterns: nearly always adherent [67.8% (63.7-71.9%) of the cohort], moderate adherence [26.6% (23.0-30.1%)], and low adherence [5.6% (4.1-7.2%)]. People were more likely to belong to the "nearly always adherent" trajectory if they were older (per additional year of age), treated with an INSTI regimen, and on treatment for more than 6 months. Our study demonstrates that the 360-day adherence to cART is generally high, but approximately one-third maintain a moderate or low adherence pattern. The use of INSTI regimens and additional support of treatment adherence, especially among younger people and those initiating therapy, may further improve adherence.

A necessidade de estocagem de alimentos para utilizacao em um maior periodo de tempo e um fator determinante para o desenvolvimento de tecnicas que preservem ao maximo a qualidade sensorial e nutricional dos produtos alimenticios mantendo-os seguros para o consumo. Diante disso, o objetivo do estudo foi realizar uma revisao de literatura sobre as principais tecnicas de conservacao dos alimentos. Utilizou-se como processo metodologico uma revisao do tipo narrativa, incluindo as bases de dados Scielo, Biblioteca Virtual em Saude (BVS), PubMed, revistas eletronicas de saude, alem de busca manual, onde foram inseridos livros e textos presentes em manuais vinculados ao ministerio da agricultura. Entre as tecnicas mais empregadas, se fez necessario uma subclassificacao, de acordo com os metodos empregados, sendo eles: preservacao por calor, frio, secagem ou desidratacao, adicao de elementos, fermentacao, osmose e acao de embalagens. Evidenciando-se que ha uma ampla variedade de metodos e tecnicas empregadas na conservacao de alimentos, muitas dessas que se iniciaram de forma rustica e atraves da modernizacao, tornaram-se mais eficientes e sofisticadas.

Key Points Question Do inpatients with supplemental private insurance coverage have higher rates of low-value services than those without private insurance in Australian public hospitals? Findings In this cross-sectional study of 219 862 inpatients, large variations in rates of low-value services were observed across hospitals. Overall, private insurance was not associated with the receipt of low-value services; however, a small number of outlying hospitals had higher rates of low-value services among privately insured patients. Meaning These results suggest that reducing low-value services requires investigating these practices at the hospital level., This cross-sectional study compares rates at which low-value services were used for adult inpatients with private vs public insurance in public hospitals in New South Wales, Australia., Importance Low-value services have limited or no benefit to patients. Rates of low-value service in public hospitals may vary by patient insurance status, given that there may be different financial incentives for treatment of privately insured patients. Objective To assess the variation in rates of 5 low-value services performed in Australian public hospitals according to patient funding status (ie, private or public). Design, Setting, and Participants This retrospective cross-sectional study analyzed New South Wales public hospital data from January 2013 to June 2018. Patients included in the sample were over age 18 years and eligible to receive low-value services based on diagnoses and concomitant procedures. Data analysis was conducted from June to December 2020. Main Outcomes and Measures Hospital-specific rates of low-value knee arthroscopic debridement, vertebroplasty for osteoporotic spinal fractures, hyperbaric oxygen therapy, oophorectomy with hysterectomy, and laparoscopic uterine nerve ablation for chronic pelvic pain were measured. For each measure, rates within each public hospital were compared by patient funding status descriptively and using multilevel models. Results A total of 219 862 inpatients were included in analysis from 58 public hospitals across the 5 measures. A total of 38 365 (22 904 [59.7%] women; 12 448 [32.4%] aged 71-80 years) were eligible for knee arthroscopic debridement for osteoarthritis; 2520 (1924 [76.3%] women; 662 [26.3%] aged 71-80 years), vertebroplasty for osteoporotic spinal fractures; 162 285 (82 046 [50.6%] women; 28 255 [17.4%] aged 61-70 years), hyperbaric oxygen therapy; 15 916 (7126 [44.8%] aged 41-50 years), oophorectomy with hysterectomy; and 776 (327 [42.1%] aged 18-30 years), uterine nerve ablation for chronic pelvic pain. Overall rates of low-value services varied considerably between measures, with the lowest rate for hyperbaric oxygen therapy (0.3 procedures per 1000 inpatients [47 of 158 220 eligible inpatients]) and the highest for vertebroplasty (30.8 procedures per 1000 eligible patients [77 of 2501 eligible inpatients]). There was significant variation in rates between hospitals, with a few outlying hospitals (ie

Refereed/Peer-reviewed Australia spends more than $20 billion annually on medicines, delivering significant health benefits for the population. However, inappropriate prescribing and medicine use also result in harm to individuals and populations, and waste of precious health resources. Medication data linked with other routine collections enable evidence generation in pharmacoepidemiology; the science of quantifying the use, effectiveness and safety of medicines in real-world clinical practice. This review details the history of medicines policy and data access in Australia, the strengths of existing data sources, and the infrastructure and governance enabling and impeding evidence generation in the field. Currently, substantial gaps persist with respect to cohesive, contemporary linked data sources supporting quality use of medicines, effectiveness and safety research; exemplified by Australia's limited capacity to contribute to the global effort in real-world studies of vaccine and disease-modifying treatments for COVID-19. We propose a roadmap to bolster the discipline, and population health more broadly, underpinned by a distinct capability governing and streamlining access to linked data assets for accredited researchers. Robust real-world evidence generation requires current data roadblocks to be remedied as a matter of urgency to deliver efficient and equitable health care and improve the health and well-being of all Australians.

BackgroundChronic obstructive pulmonary disease (COPD) has an appreciable socioeconomical impact in low- and middle-income countries, but most epidemiological data originate from high-income countries. For this reason, it is especially important to understand survival and factors associated with survival in COPD patients in these countries.ObjectiveTo assess survival of COPD patients in Brazil, to identify risk factors associated with overall survival, including treatment options funded by the Brazilian National Health System (SUS).MethodologyWe built a retrospective cohort study of patients dispensed COPD treatment in SUS, from 2003 to 2015 using a National Database created from the record linkage of administrative databases. We further matched patients 1:1 based on sex, age and year of entry to assess the effect of the medicines on patient survival. We used the Kaplan-Meier method to estimate overall survival of patients, and Cox's model of proportional risks to assess risk factors.ResultThirty seven thousand and nine hundred and thirty eight patients were included. Patient's survival rates at 1 and 10 years were 97.6% (CI 95% 97.4–97.8) and 83.1% (CI 95% 81.9–84.3), respectively. The multivariate analysis showed that male patients, over 65 years old and underweight had an increased risk of death. Therapeutic regimens containing a bronchodilator in a free dose along with a fixed-dose combination of corticosteroid and bronchodilator seem to be a protective factor when compared to other regimens.ConclusionOur findings contribute to the knowledge of COPD patients' profile, survival rate and related risk factors, providing new evidence that supports the debate about pharmacological therapy and healthcare of these patients.

Background Low value care (LVC) services have limited or no benefit to patients, and curtailing LVC can curb unnecessary spending and improve the quality of care. Some public hospitals in Australia have financial incentives to perform procedures for patients with private health insurance, yet little is known if there are differences in LVC between public and private patients. Methods We performed a retrospective analysis of New South Wales public hospital data from January 2013 to June 2018. We measured hospital-specific rates of five LVC services and compared rates within each public hospital by patient funding status (private or public), descriptively and using random-slope multilevel models. Results Overall rates of LVC varied between services, ranging from 0.3 to 30.8 procedures per 1,000 eligible patients for hyperbaric oxygen therapy and vertebroplasty, respectively. There was large variation in rates of the LVC services between hospitals, and a few hospitals had higher rates of LVC among private than public patients. However, we found no consistent association between patient funding status and LVC services: private patients had lower rates of knee arthroscopic debridement than public patients (aOR:0.56) and higher rates of low value vertebroplasty for osteoporotic spinal fractures (aOR:1.08), hyperbaric oxygen therapy (aOR:1.53) and oophorectomy (aOR:1.77); all statistically non-significant. Conclusions Private patient funding may contribute to LVC in some public hospitals, but it was not consistently associated with higher rates of the five LVC services measured. Key messages Reducing LVC services requires investigating the role of health-system factors at both the global- and local-level.

Health-related quality of life (HRQoL) is a multidimensional concept involving an individual's self-perception about how a disease or treatment impacts their daily life. In this study, we evaluated the HRQoL and factors associated with this outcome in 366 patients initiating combination Antiretroviral Therapy (cART) in Belo Horizonte, Brazil.We measured HRQoL using the EuroQoL-5D 3 level (EQ-5D) and the HIV instrument of the World Health Organization (WHOQOL-HIV BREF) and identified factors associated with HRQoL using multilevel linear regression. Participants had been on cART treatment a median of 65.5 days at the time the instruments were completed. The median HRQoL of patients on the single-tablet regimen containing efavirenz/ tenofovir/ lamivudine and the multi-tablet regimen containing dolutegravir and tenofovir/ lamivudine were high, with no significant difference between groups. Factors consistently associated with lower HRQoL were being single (unmarried), having a lower educational level, recent cigarette smoking, recent signs and symptoms of anxiety or depression, comorbid disease and the occurrence of adverse drug reactions. We observed high levels of HRQoL in cART-treated people and no differences between dolutegravir and efavirenz-based regimens. This study provides inputs to future economic analysis and identifies opportunities to increase the HRQoL of patients by targeting modifiable factors.

Os Disruptores Endocrinos (DEs) sao substâncias que influenciam nas atividades orgânicas do sistema endocrino do corpo humano. Nas ultimas decadas, tem-se aumentado o interesse da comunidade cientifica e da midia acerca dos possiveis efeitos danosos causados aos seres humanos pela exposicao a essas substâncias quimicas. Este estudo objetivou realizar uma revisao de literatura sistematica sobre os conceitos destas substâncias quimicas, seus efeitos na saude humana e mecanismo de acao. Foi realizado um levantamento bibliografico por meio das bases de dados Biblioteca Virtual em Saude (BVS) e Scielo, site institucional e livros entre os anos de 1999 e 2019, nos idiomas portugues e ingles. Os dados obtidos indicaram o impacto dos DEs na obesidade, diabetes, sistema cardiovascular, sindrome dos ovarios policisticos, carcinogenicidade e sistema tireoideano. Logo, os DEs sao substâncias que afetam a saude humana, uma vez que, varios estudos indicam interferencia endocrina dessas substâncias, as quais repercutem em danos ao organismo.

ObjectiveA wealth of data is generated through Australia’s universal health care arrangements. However, use of these data has been hampered by different federal and state legislation, privacy concerns and challenges in linking data across jurisdictions. A series of data reforms have been touted to increase population health research capacity in Australia, including pharmacoepidemiology research. Here we catalogued research leveraging Australia’s Pharmaceutical Benefits Scheme (PBS) data (2014–2018) and discussed these outputs in the context of previously implemented and new data reforms. MethodsWe conducted a systematic review of population-based studies using PBS dispensing claims. Independent reviewers screened abstracts of 4,996 articles and 310 full-text manuscripts. We characterised publications according to study population, analytical approach, data sources used, aims and medicines focus. ResultsWe identified 180 studies; 133 used individual-level data, 70 linked PBS dispensing claims with other health data (66 across jurisdictions). Studies using individual-level data focussed on Australians receiving government benefits (87 studies) rather than all PBS-eligible persons. 63 studies examined clinician or patient practices and 33 examined exposure-outcome relationships (27 evaluated medicines safety, 6 evaluated effectiveness). Medicines acting on the nervous and cardiovascular system account for the greatest volume of PBS medicines dispensed and were the most commonly studied (67 and 40 studies, respectively). Antineoplastic and immunomodulating agents account for approximately one third of PBS expenditure but represented only 10% of studies in this review. ConclusionsThe studies in this review represent more than a third of all population-based pharmacoepidemiology research published in the last three decades in Australia. Recent data reforms have contributed to this escalating output. However, studies are concentrated among specific subpopulations and medicines classes, and there remains a limited understanding of population benefits and harms derived from medicines use. The current draft Data Availability and Transparency legislation should further bolster efforts in population health research.

Objetivos: Avaliar a eficácia da terapia dupla em indivíduos submetidos à troca, mantendo carga viral < 50 cópias/ml e em casos de troca por insuficiência renal, se houve alteração no clearance de cretinina, creatinina sérica e fósforo sérico. Metodologia: Coorte retrospectiva de indivíduos > 18 anois, que mudaram para terapia dupla, acompanhados por até 116 semanas e os resultados foram avaliados em 48 e/ou até 96 semanas após a troca. Os dados foram coletados no período de julho de 2020 a junho de 2021, por meio de pronbtuários e consulta so Sistema de Controle de Exames Laboratoriais (SISCEL) e ao Sistema de Controle Logístico de Medicamentos (SICLOM). As análises foram realizadas utilizando o software SPSS. Resultados: A maioria dos indivíduos era do sexo masculino (65,5%), a média de idade na troca foi de 54,4 anos. O esquema de terapia dupla mais utilizado foi a associação DTG + 3TC (73,6%). O principal motivo de troca foi função renal prejudicada (40%), o medicamento mais descontinuado foi o TDF (55,79%). A maioria dos indivíduos manteve a supressão viral por até 48 semanas após a troca (n=84, 96,8%). Dois indivíduos (2,3%) não atingiram supressão viral neste período, com valores de 51 e 55 cópias/ml de vírus. Não houve alteração significativa na TFG comparando os níveis basais com 48 semanas após a troca. Quanto ao fósforo, comparando o valor basal, com o valor medido 48-96 semans após a troca houve discreto aumento, com significância estatística (2,70 ± 0,76 mg/dl vs. 3,14 ± 0,47; p = 0,026). Conclusão: A maioria dos indivíduos manteve a supressão viral em até 48 e/ou até 96 semanas, demonstrando efetividade da terapia dupla. Entre os que trocaram por insuficiência renal, não houve melhora da taxa de filtração glomerular em 48 semans, mas observou-se aumento da excreção de fósforo, o que requer mais estudos, com amostra maior e seguimento mais longo.

Introduction: There are positive aspects regarding the prescribing of fixed-dose combinations (FDCs) versus prescribing the medicines separately. However, these have to be balanced against concerns including increased costs and their irrationality in some cases. Consequently, there is a need to review their value among lower and middle income countries (LMICs) which have the greatest prevalence of both infectious and non-infectious diseases and issues of affordability. Areas covered: Review of potential advantages, disadvantages, cost-effectiveness and availability of FDCs in high priority disease areas in LMICs and possible initiatives to enhance the prescribing of valued FDCs and limit their use where concerns with their value. Expert commentary: FDCs are valued across LMICs. Advantages include potentially improved response rates, reduced adverse reactions, increased adherence rates and reduced costs. Concerns include increased chances of drug:drug interactions, reduced effectiveness, potential for imprecise diagnoses and higher unjustified prices. Overall certain FDCs including those for malaria, tuberculosis and hypertension are valued and listed in country’s essential medicine lists, with initiatives needed to enhance their prescribing where currently low prescribing rates. Proposed initiatives include robust clinical and economic data to address the current paucity of pharmacoeconomic data. Irrational FDCs persists in some countries which is being addressed.

Combination Antiretroviral Therapy (cART) in single-tablet regimens (STR) is a simplification strategy that can potentially improve medication adherence and clinical outcomes. We conducted a retrospective cohort study of 1206 patients using efavirenz, tenofovir and lamivudine in multiple-tablet regimen who switched to the STR containing the same active ingredients in a southeast metropolis in Brazil. We measured adherence using the proportion of days covered (PDC≥95%) and evaluated this outcome before and after the switch using paired non-parametric statistics. Additionally, we used group-based trajectory modeling to identify adherence patterns to cART for each period and evaluate the migration behavior of patients between the trajectory groups. We observed a 14% increase in the proportion of adherent patients after switching to STR and a 6.2% increase in the proportion of patients with CD4 count500 cells/μl (

Background Schizophrenia is associated with significant economic burden. In Brazil, antipsychotic drugs and outpatient and hospital services are provided by the Brazilian National Health System (SUS) for patients with schizophrenia. However, few studies capture the cost of managing these patients within the Brazilian NHS. This is important to appraise different management approaches within universal healthcare systems. Objective Our objective was to use real-world data to describe the costs associated with the treatment of schizophrenia in adults receiving atypical antipsychotics in Brazil from 2000 to 2010. Methods We integrated three national databases for adult patients with schizophrenia receiving one or more atypical antipsychotics. We assessed only direct medical costs and the study was conducted from a public-payer perspective. A multivariate log-linear regression model was performed to evaluate associations between costs and clinical and demographic variables. Results We identified 174,310 patients with schizophrenia, with mean ± standard deviation (SD) annual costs of $US1811.92 ± 284.39 per patient. Atypical antipsychotics accounted for 79.7% of total costs, with a mean annual cost per patient of $US1578.74 ± 240.40. Mean annual costs per patient were $US2482.90 ± 302.92 for psychiatric hospitalization and $US862.96 ± 160.18 for outpatient psychiatric care. Olanzapine was used by 47.7% of patients and represented 62.8% of the total costs of atypical antipsychotics. Patients who used clozapine had the highest mean annual cost per patient for outpatient psychiatric care and psychiatric hospitalization. Conclusions Atypical antipsychotics were responsible for the majority of the schizophrenia treatment costs, and psychiatric hospitalization costs were the highest mean annual cost per patient. Authorities should ensure efficient use of atypical antipsychotics and encourage outpatient psychiatric care over psychiatric hospitalization where possible. Electronic supplementary material The online version of this article (10.1007/s40258-018-0408-4) contains supplementary material, which is available to authorized users.

To evaluate the prevalence of adverse drug reactions (ADR) and associated factors during the use of Highly Active Antiretroviral Therapy (HAART) in patients initiating treatment. This is a cross-sectional analysis of a prospective study conducted in three public referral services specialized in HIV/AIDS care in Belo Horizonte, Brazil. Self-reported ADR and explanatory variables were obtained from face-to-face interview and from Information Systems. Associated factors with ADR were evaluated by logistic regression in SPSS software v.22. We included 399 patients, of which 85.5% reported at least one and 72.7% up to 5 ADRs after HAART initiation. Neurological reactions were the most frequent, with self-reported ADRs being distinct according to HAART regimen used. The global model showed higher chance of ADRs among females (OR = 3.52) and illicit drug users (OR = 2.28). Lower chance of ADRs was found for patients aged > 33 years (OR = 0.37), DTG/TDF/3TC users (OR = 0.41), and higher physical domain of quality of life (OR = 0.78). The model restricted to patients using the single-tablet regimen EFV/TDF/3TC showed lower ADRs among patients with CD4+ T lymphocyte count > 200 cells/mm3 (OR = 0.23) and higher independence domain of quality of life (OR = 0.74). The model restricted to DTG/TDF/3TC and to other regimens showed lower ADRs with higher physical domain of quality of life (OR = 0.74 and OR = 0.55, respectively). The prevalence of self-reported ADRs to first-line antiretroviral regimens was high and patients using DTG/TDF/3TC had a smaller number of ADRs. In addition to HAART regimen, sociodemographic, clinical, and quality of life characteristics were associated with ADRs.

OBJECTIVE: To estimate the prevalence of smoking and evaluate the factors associated with this outcome in people living with HIV (PLHIV). METHODS: This is a cross-sectional study of a prospective concurrent cohort of 462 individuals initiating antiretroviral therapy at three HIV/AIDS specialized services in Belo Horizonte between 2015 and 2017. The following smoking status were used: current smoker (CS), former smoker (FS) and non-smoker (NS). Multinomial logistic regression was performed with NS as the reference category. RESULTS: Most participants were men (81.4%), young (up to 34 years old; 57.2%) and non-white (75.7%). Of the total number of individuals, 27.7% were CS, 22.9% FS, and 49.4% NS. Most smokers were light smokers (65.1%), consumed up to 10 cigarettes per day and had been smoking for more than 10 years (63.3%), starting on average at 17.2 years of age (SD = 5.1). In the multivariate analysis, higher chances of being CS were associated with: being female, having up to 9 years of schooling, current or prior use of alcohol and illicit drugs (marijuana, cocaine and crack) and presenting signs and/or symptoms of anxiety or depression. Higher chances of being FS were associated with having up to 9 years of schooling and current or prior use of alcohol and illicit drugs (marijuana and crack). CONCLUSIONS: The results show that smoking is highly prevalent among PLHIV, indicating the need for HIV specialized services to prioritize smoking cessation interventions. These interventions should consider the use of alcohol and illicit drugs and be targeted especially to young people, those with low schooling and with signs and/or symptoms of anxiety or depression.

Introdução: A terapia antirretroviral (TARV) é um dos pilares no controle da infecção pelo Vírus da Imunodeficiência Humana (HIV) por evitar a progressão da doença e prevenir novos casos de infecção. Sua efetividade é, porém, condicionada a níveis elevados de adesão. Esquemas antirretrovirais em dose fixa combinada (DFC) são medicamentos que contém três ou mais antirretrovirais em um único comprimido, simplificando, assim, a TARV, e potencialmente propiciando melhores resultados clínicos. Desde 2015, o esquema em DFC contendo tenofovir disoproxil fumarato, lamivudina e efavirenz está disponível no Sistema Único de Saúde (SUS). Entretanto, evidências sobre os desfechos em saúde e relação de custo-efetividade com o uso desta formulação específica são escassas. Objetivo: Realizar uma análise epidemiológica e farmacoeconômica do tratamento antirretroviral em DFC em pessoas que vivem com HIV que iniciam a terapia antirretroviral no SUS. Adicionalmente, foi avaliado o perfil de utilização e de adesão à TARV no contexto australiano. Métodos: Quatro estudos foram desenvolvidos no âmbito desta tese. No Estudo 1 foi desenvolvida uma coorte prospectiva não concorrente para avaliar a efetividade do esquema em DFC comparado a múltiplos medicamentos e doses (MMD) em indivíduos acompanhados em um centro de referência em Belo Horizonte entre janeiro de 2014 e dezembro de 2016. Neste estudo, a variável resposta foi a efetividade da TARV, definida como supressão viral [carga viral (CV) < 50 cópias/ml] após seis e doze meses do início do tratamento. No Estudo 2 foi realizada uma análise de custo-efetividade na perspectiva do SUS e limitada aos custos diretos médicos para comparar os resultados dos indivíduos que iniciaram TARV em DFC ou em MMD. Foi utilizada a mesma população do Estudo 1 e foram comparados a proporção de indivíduos em supressão viral e os custos após um ano de tratamento entre os grupos. Os resultados foram expressos em dólares estadounidenses após conversão pela paridade do poder de compra (1 US$ = 1,996 R$). O Estudo 3 trata-se de um corte transversal realizado a partir da linha de base de uma coorte prospectiva em três centros de referência de Belo Horizonte, que recrutou indivíduos entre setembro de 2015 e agosto de 2017. Neste estudo foi avaliada a qualidade de vida de indivíduos iniciando a TARV por meio dos instrumentos WHOQOL-HIV bref e EuroQol-5 Dimensions. Os fatores associados a este desfecho foram avaliados por modelos de regressão linear multinível para cada instrumento utilizado. No Estudo 4 foi desenvolvida uma coorte retrospectiva de bases de dados de dispensação para avaliar o perfil de uso e de adesão dos indivíduos em uso de TARV na Austrália entre julho de 2013 e junho de 2017. A adesão foi mensurada pela proporção de dias cobertos (PDC) utilizando como ponto de corte PDC ≥ 95% e, secundariamente PDC ≥ 80%. Calcularam-se os desfechos após 12 meses de acompanhamento e em intervalos mensais para permitir a modelagem de trajetória baseada em grupo. Resultados: No Estudo 1 foram incluídos 440 indivíduos, dos quais a maior parte (58%) iniciou a TARV em esquemas MMD. A supressão viral foi de 74,6% aos seis meses e de 83,2% aos doze meses, sendo maior entre aqueles que utilizaram DFC apenas aos seis meses (p < 0,05). Fatores associados à menor probabilidade de supressão viral variaram aos seis e doze meses, incluindo em pelo menos um dos tempos de avaliação a CV inicial ≥ 100.000 cópias/ml, presença de sinais e sintomas definidores de aids, registro de troca de antirretroviral, maior intervalo de tempo entre diagnóstico e início da TARV e o consumo de tabaco ou drogas ilícitas durante o acompanhamento. O registro de adesão à TARV e pertencer à categoria de risco/exposição de homens que fazem sexo com homens foram associados à maior probabilidade de efetividade. O Estudo 2 identificou o esquema em DFC como a escolha ideal entre as terapias disponíveis no Brasil entre 2014 e 2016, com custo médio anual de US$ 1.101,65 (DP 2.775,68) e menor relação de custo-efetividade após um ano de acompanhamento. No Estudo 3 foram incluídos 366 participantes. A mediana de qualidade de vida foi acima de 80% para todos os instrumentos utilizados, sem diferenças entre indivíduos que utilizaram esquemas contendo dolutegravir ou efavirenz, ambos associados à tenofovir disoproxil fumarato/ lamivudina. Os seguintes fatores foram associados à pior QV em pelo menos dois dos três modelos desenvolvidos: estado civil (não casado), ter menor nível educacional, reportar tabagismo recente, sinais e sintomas recentes de ansiedade ou depressão, comorbidades e ocorrência de reações adversas a medicamentos. No Estudo 4 foram incluídos 2.107 participantes, a maior parte em uso de esquemas contendo 2 inibidores da transcriptase reversa análogos de nucleosídeos/nucleotídeos associados a um inibidor da transcriptase reversa não análogos de nucleosídeos (44,6%). Após um ano de seguimento, o PDC médio foi de 81,0% (DP 21,2) e a proporção de pessoas que aderiu à TARV foi de 35,7% utilizando o limiar de PDC 95% e de 60,9% utilizando o limiar de PDC 80%. A análise de trajetória revelou três padrões para a probabilidade de adesão ao longo do tempo: boa adesão, baixa adesão e não-adesão precoce, sendo que apenas 51,7% dos participantes pertencia ao grupo de boa adesão. Os fatores associados à maior probabilidade de pertencer a este grupo foram idade mais avançada e o uso de esquemas contendo inibidores da integrase. Padrões semelhantes foram obtidos para o limiar de PDC 80%. Conclusões: A disponibilização do esquema em DFC no Brasil apresentou benefícios quanto à efetividade e relação de custo-efetividade. Este esquema deveria, portanto, ser utilizado como comparador para fins de futuras incorporações de antirretrovirais de primeira linha no país. Até o momento, esquemas mais novos, contendo inibidores da integrase não apresentaram benefícios quanto à qualidade de vida no contexto brasileiro, embora estudos longitudinais que avaliem este e demais desfechos devam ser realizados. De maneira geral, pessoas que vivem com HIV em Belo Horizonte, e que iniciaram a TARV, apresentam elevada incidência de supressão viral aos seis e doze meses, bem como elevada qualidade de vida. Entretanto, é possível melhorar estes resultados por meio do diagnóstico e início precoce da TARV, intensificação do aconselhamento dos profissionais de saúde sobre eventos adversos, incentivo à adesão dos pacientes, triagem e apoio psicológico para indivíduos com ansiedade ou depressão, e redução do uso de substâncias (tabaco e drogas ilícitas) nesta população. Independentemente do ponto de corte para uma adesão ideal, apenas metade das pessoas em tratamento antirretroviral mantêm uma boa adesão ao longo do tempo no contexto australiano, ressaltando o caráter dinâmico e complexo da adesão a medicamentos de uso crônico. Os resultados corroboram o uso de medicamentos com menor incidência de reações adversas e acompanhamento regular da adesão ao tratamento, especialmente entre indivíduos mais jovens. Background: The combination antiretroviral therapy (cART) is the main strategy to control the Human Immunodeficiency Virus (HIV) infection, preventing the progression of the disease and the transmission of the virus. Its effectiveness, however, depends on high levels of adherence. Single-tablet regimens (STRs) contain three or more antiretrovirals in a singletablet, thus simplifying cART, and potentially providing better clinical outcomes. Since 2015, the STR regimen containing tenofovir disoproxil fumarate, lamivudine and efavirenz is available in the Brazilian National Health System (SUS). However, evidence on the health outcomes and cost-effectiveness with the use of this specific formulation is lacking. Objective: To conduct an epidemiological and pharmacoeconomic analysis of antiretroviral treatment in STR among people living with HIV who initiate cART in SUS. In addition, we evaluated the patterns of use and adherence to cART in the Australian context. Methods: We developed four studies within this thesis. In Study 1, we developed a nonconcurrent prospective cohort to evaluate the efficacy of STR compared to multiple tablet regimens (MTR) in subjects followed at a referral center in Belo Horizonte between January 2014 and December 2016. In this study, the response variable was the effectiveness of ART, defined as viral suppression [viral load (VL) < 50copies/ml] six and twelve months after initiating the treatment. In Study 2, a cost-effectiveness analysis was performed from the SUS perspective and limited to direct medical costs to compare the results of individuals who initiated cART in STR or MTR. We included the same population of Study 1 and compared the proportion of patients achieving viral suppression and associated costs after one year of follow-up between the groups. Results were expressed in United States dollars after conversion by the purchase power parity (US$ 1 = R$ 1,996). Study 3 is a cross-sectional analysis from the baseline of a prospective cohort study conducted at three reference centers in Belo Horizonte, Brazil, which recruited individuals between September 2015 and August 2017. We evaluated the Health-Related Quality of Life (HRQoL) of individuals initiating cART using the WHOQOL-HIV bref and EuroQol-5 Dimensions instruments. The factors associated with this outcome were evaluated by multilevel linear regression models for each instrument. In Study 4, a retrospective cohort of dispensing databases was developed to assess patterns of use and adherence to cART in Australia between July 2013 and June 2017. Adherence was measured by the proportion of days covered (PDC) using a cutoff of PDC ≥ 95% and, secondarily, PDC ≥ 80%. The outcomes were calculated after 12 months of followup and at monthly intervals to allow group-based trajectory modeling. Results: Study 1 included 440 patients, of whom the majority (58%) initiated cART in MTRs. The viral suppression was 74.6% at six months and 83.2% at twelve months, being higher among patients who used STR only at six months (p < 0.05). Factors associated with a lower probability of viral suppression included baseline VL ≥ 100,000 copies/ml, presence of AIDS-defining signs and symptoms, antiretroviral switch, longer interval between diagnosis and cART initiation, and use of tobacco or illicit drugs during the follow-up. Adherence to cART and belonging to the category of risk/exposure of men who have sex with men were associated with a greater probability of effectiveness. Study 2 identified the STR as the optimal choice among the therapies available in Brazil between 2014 and 2016, with an annual cost of US$ 1,101.65 (SD 2,775.68) and a lower cost-effectiveness ratio after one year of follow-up. Study 3 included 366 participants, which showed a median quality of life over 80% for all instruments used. There were no differences between subjects using dolutegravir or efavirenz regimens, both with the backbone tenofovir disoproxil fumarate/ lamivudine. The following factors were associated with poorer HRQoL in at least two of the three models developed: civil status (unmarried), lower educational level, recent cigarette smoking, recent signs and symptoms of anxiety or depression, comorbidities, and occurrence of adverse drug reactions. In Study 4, we included 2,107 participants, most of them using cART regimens containing 2 Nucleoside/Nucleotide Reverse Transcriptase Inhibitors + Non-Nucleoside Reverse Transcriptase Inhibitor (44.6%). After one year of follow-up, the mean PDC was 81.0% (SD 21.2) and the proportion of people adherent to ART was 35.7% using the 95% PDC threshold and 60.9% using the 80% PDC threshold. The trajectory analysis revealed three patterns for the probability of adherence over time: good adherence, low adherence, and early non-adherence, and only 51.7% of the participants belonged to the good adherence group. The factors associated with a higher probability of belonging to this group were older age and the use of integrase inhibitors regimens. Similar patterns were obtained for the 80% PDC threshold. Conclusions: The availability of STR in Brazil was beneficial in terms of effectiveness and cost-effectiveness. Therefore, this regimen should be used as a comparator for the purpose of future incorporations of first-line antiretrovirals in the country. To date, newer regimens containing integrase inhibitors have not shown any benefits on HRQoL in the Brazilian context, although longitudinal studies evaluating this and other outcomes should be performed. In general, people living with HIV in Belo Horizonte, who initiated cART, have a high incidence of viral suppression at six and twelve months, as well as high quality of life. However, it is possible to improve these results through early diagnosis and initiation of cART, intensification of health professionals' counseling on adverse events, encouraging patient adherence to cART, increasing the screening and the psychological support for individuals with anxiety or depression, and reducing the use of substances (tobacco and illicit drugs) in this population. Regardless of the cutoff point for optimal adherence, only half of the people on cART maintain good adherence over time in the Australian context, emphasizing the dynamic and complex character of adherence to chronic medications. The results corroborate the use of cART with a lower incidence of adverse drug reactions and regular follow-up of adherence to treatment, especially among younger individuals.